Elucidation of the Interaction Mechanism with Liposomes of gH625-Peptide Functionalized Dendrimers

Falanga, Annarita; Tarallo, Rossella; Carberry, Thomas; Galdiero, Massimiliano; Weck, Marcus; Galdiero, Stefania

doi:10.1371/journal.pone.0112128

Cited by 24 publications

(25 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The gH625-dendrimer presents a high affinity for the membrane bilayer and deeply penetrates the bilayer where it does not form holes. 20 Our previous data support the hypothesis that the interaction with the bilayer can be splitted into a rst adsorption step that leads to an increased macromolecule concentration on the membrane and a second insertion step which involves the penetration into the lipid bilayer and likely a conformational change of the peptide bound to the dendrimer which assumes a helical conformation when in a membrane mimetic environment. Clearly, the mechanism of lipid association is key in the translocation process and thus in cellular uptake.…”

Section: Introductionsupporting

confidence: 79%

“…Further structural characterization to conrm the functionalization were performed as previously reported. 20…”

Section: Peptide-dendrimer Preparationmentioning

confidence: 99%

“…The peptide gH625 is derived from herpes simplex virus 1 and was developed in our research group as the rst membranotropic sequence able to enhance drug delivery. [16][17][18][19] We also previously reported on a poly(amide)-based dendrimer [20][21][22] coupled to gH625, showing its ability to cross the membrane bilayer through an energy-independent process, without evidence of endocytosis, poration, or cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The intriguing journey of gH625-dendrimers

et al. 2017

View full text Add to dashboard Cite

The knowledge of the mechanism used by vectors to gain access to cell interiors is key to the development\ud of effective drug delivery tools for different pathologies. The role of the initial interaction with the\ud membrane bilayer is widely recognized, although not fully understood. We use neutron reflectivity\ud experiments and internalization studies with cells to reveal the extent of interaction of dendrimers\ud functionalized with the peptide gH625 with biomimetic membranes. We further investigate the\ud internalization by use of Caco-2 cells for assessing the membrane permeability properties of the\ud peptide–dendrimer construct. Neutron reflectivity allowed for the hypothesis that the peptide–\ud dendrimer is able to pass across the bilayer which was confirmed via permeability studies. We find that\ud gH625-dendrimers interact more strongly with cholesterol containing membranes. The advances in our\ud understanding of the mechanism of drug uptake are extremely useful to push further the design of new\ud drug delivery systems

show abstract

Section: Introductionsupporting

confidence: 79%

“…Further structural characterization to conrm the functionalization were performed as previously reported. 20…”

Section: Peptide-dendrimer Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The intriguing journey of gH625-dendrimers

et al. 2017

View full text Add to dashboard Cite

show abstract

“…10,11 This peptide has proved to exhibit exceptional vector properties 9 and has been shown to be essentially internalized by a nonendocytic pathway avoiding endosomal entrapment. 7,[12][13][14][15][16][17] In recent studies, it was also shown to be able to cross the blood-brain barrier in vitro and in vivo. 18 gH625 is, therefore, a very good delivery vector 9 and its coupling to NPs may be exploited to change their internalization mechanism and in case of MNPs, to avoid or reduce their toxicity.…”

Section: Introductionmentioning

confidence: 99%

<em>Daphnia magna</em> and<em> Xenopus laevis</em> as in vivo models to probe toxicity and uptake of quantum dots functionalized with gH625

Galdiero¹,

Falanga²,

Siciliano³

et al. 2017

IJN

Self Cite

View full text Add to dashboard Cite

The use of quantum dots (QDs) for nanomedicine is hampered by their potential toxicologic effects and difficulties with delivery into the cell interior. We accomplished an in vivo study exploiting Daphnia magna and Xenopus laevis to evaluate both toxicity and uptake of QDs coated with the membranotropic peptide gH625 derived from the glycoprotein H of herpes simplex virus and widely used for drug delivery studies. We evaluated and compared the effects of QDs and gH625-QDs on the survival, uptake, induction of several responsive pathways and genotoxicity in D. magna , and we found that QDs coating plays a key role. Moreover, studies on X. laevis embryos allowed to better understand their cell/tissue localization and delivery efficacy. X. laevis embryos raised in Frog Embryo Teratogenesis Assay- Xenopus containing QDs or gH625-QDs showed that both nanoparticles localized in the gills, lung and intestine, but they showed different distributions, indicating that the uptake of gH625-QDs was enhanced; the functionalized QDs had a significantly lower toxic effect on embryos’ survival and phenotypes. We observed that D. magna and X. laevis are useful in vivo models for toxicity and drug delivery studies.

show abstract

“…One of the main applications of fusion peptides of enveloped viruses is as inhibitors of viral penetration. Their ability to directly interact with the hydrophobic surfaces present on cell membranes and/or fusion proteins allows them to interfere with virus entry . The inhibition mechanism is still unclear but it is likely that inhibition of infectivity is correlated to inactive aggregates formed between the fusogenic stretches present in the viral protein and in the peptides.…”

Section: Applications Of Membranotropic Peptidesmentioning

confidence: 99%

Membranotropic peptides mediating viral entry

et al. 2018

Self Cite

View full text Add to dashboard Cite

The means used by enveloped viruses to bypass cellular membranes are well characterized; however, the mechanisms used by non‐enveloped viruses to deliver their genome inside the cell remain unresolved and poorly defined. The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. Thus, in spite of noticeable differences in entry, this short stretches of membranotropic peptides are probably associated with similar entry‐related events. This review will uncover the intrinsic features of viral membranotropic peptides involved in viral entry of both naked viruses and the ones encircled with a biological membrane with the objective to better elucidate their different functional properties and possible applications in the biomedical field.

show abstract

Elucidation of the Interaction Mechanism with Liposomes of gH625-Peptide Functionalized Dendrimers

Cited by 24 publications

References 71 publications

The intriguing journey of gH625-dendrimers

The intriguing journey of gH625-dendrimers

<em>Daphnia magna</em> and<em> Xenopus laevis</em> as in vivo models to probe toxicity and uptake of quantum dots functionalized with gH625

Membranotropic peptides mediating viral entry

Contact Info

Product

Resources

About